title: ERF and ETV3L are retinoic acid-inducible repressors required for primary neurogenesis.
abstract: Cells in the developing neural tissue demonstrate an exquisite balance between proliferation and differentiation. Retinoic acid (RA) is required for neuronal differentiation by promoting expression of proneural and neurogenic genes. We show that RA acts early in the neurogenic pathway by inhibiting expression of neural progenitor markers Geminin and Foxd4l1, thereby promoting differentiation. Our screen for RA target genes in early Xenopus development identified Ets2 Repressor Factor (Erf) and the closely related ETS repressors Etv3 and Etv3-like (Etv3l). Erf and Etv3l are RA responsive and inhibit the action of ETS genes downstream of FGF signaling, placing them at the intersection of RA and growth factor signaling. We hypothesized that RA regulates primary neurogenesis by inducing Erf and Etv3l to antagonize proliferative signals. Loss-of-function analysis showed that Erf and Etv3l are required to inhibit proliferation of neural progenitors to allow differentiation, whereas overexpression of Erf led to an increase in the number of primary neurons. Therefore, these RA-induced ETS repressors are key components of the proliferation-differentiation switch during primary neurogenesis in vivo.
authors.affiliation: Department of Developmental and Cell Biology, 2011 Biological Sciences 3, University of California, Irvine, CA 92697-2300, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Janesick
authors.forename: Rachelle
authors.initials: R
authors.lastname: Abbey
authors.forename: Connie
authors.initials: C
authors.lastname: Chung
authors.forename: Sophia
authors.initials: S
authors.lastname: Liu
authors.forename: Mao
authors.initials: M
authors.lastname: Taketani
authors.forename: Bruce
authors.initials: B
authors.lastname: Blumberg
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation; D049109:Cell Proliferation; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology; D055785:Gene Knockdown Techniques; D017403:In Situ Hybridization; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014212:Tretinoin / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000502:physiology*
chemical_list: C583605:ERF protein, Xenopus; C583606:ETV3L protein, Xenopus; D050783:Proto-Oncogene Proteins c-ets; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D029867:Xenopus Proteins; D014212:Tretinoin; D005346:Fibroblast Growth Factors
keywords: Differentiation; Ets repressors; Neural progenitor; Primary neurogenesis; Proliferation; Retinoic acid; Xenopus